期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.703931
关键词
NMOSD; tocilizumab; B cells; T helper cells; PD-1; PD-L
类别
资金
- National Natural Science Foundation of China [81601019, 81601039, 82071389]
- Natural Science Foundation of Tianjin Province [20JCJQJC00280, 18JCQNJC13200, 20JCQNJC00460]
Tocilizumab demonstrated therapeutic efficacy on NMOSD by enhancing B- and T-cell homeostasis through regulating B-cell differentiation and inhibiting lymphocyte activation. In NMOSD patients, the drug led to a shift of B cells to naive B cells from memory B cells after 3 months, as well as downregulating markers associated with T-cell activation on B cells. This study also showed a decrease in total Tfh and Tph cells frequency and an increase in follicular regulatory T cells, while restoring PD-L1 selectively on B-cell subsets.
Tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, showed its therapeutic efficacy on neuromyelitis optica spectrum disorder (NMOSD). To assess the immunological effects of this drug on B cells, follicular T helper (Tfh) cells, and peripheral T helper (Tph) cells in patients with NMOSD, peripheral B cell and Tfh cell phenotypes were evaluated in 26 patients with NMOSD before and after tocilizumab treatment by nine-color flow cytometry, as well as the expression of costimulatory and co-inhibitory molecules on B cells. Results showed that the frequency of CD27(+)IgD(-) switched memory B cells, CD27(-)IgD(-) double-negative B cells, and CD27(high) CD38(high) antibody-secreting cells was increased in patients with NMOSD. Tocilizumab treatment led to a significant shift of B cells to naive B cells from memory B cells after 3 months. Three markers on B cells associated with T-cell activation (i.e., CD86 CD69, and HLA-DR) were downregulated after tocilizumab treatment. The frequencies of total Tfh and Tph cells were decreased, whereas that of follicular regulatory T cells tended to increase. Intrinsic increased PD-L1 and PD-L2 expression was characteristic of B cells in patients with NMOSD. Tocilizumab selectively restored PD-L1 on B-cell subsets. These results provided evidence that tocilizumab enhanced B- and T-cell homoeostasis by regulating B-cell differentiation and inhibiting lymphocyte activation in patients with NMOSD.
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